PROJECT SUMMARY/ABSTRACT Chronic kidney disease (CKD) is a global public health epidemic, affecting 10-16% of the adult population in Asia, Europe, and North America. The clinical impact of CKD is substantial: risks of end stage renal disease (ESRD), cardiovascular disease (CVD), and premature mortality are all heightened, but options for CKD prevention and treatment remain limited. The proposed study is a renewal of R01 DK100446, a grant which funds the CKD Prognosis Consortium (CKD-PC). CKD-PC was formed in 2009 and now includes data on >11 million participants from more than 70 cohorts spanning 40 countries with a strong track record of producing high impact meta-analyses (2 in NEJM, 3 in Lancet, 4 in JAMA, 1 in BMJ, 4 in Kidney Int, 2 in JASN, 2 in AJKD, and 1 in Lancet Diabetes Endocrinol). CKD-PC complements established cohorts in CKD by representing a broad range of global populations; spanning the full range of kidney function; devoting tenacious attention to harmonization, exploration of heterogeneity, and calibration; and meta-analyzing results where appropriate. In this new funding period, we will continue to mentor and recruit investigators and cohorts from around the world, grow substantially, and innovate with new areas of emphasis in the following aims: Aim 1. To determine risk of incident CKD and CKD progression associated with clinical markers across a range of patient populations. Aim 2. To evaluate the risk of non-kidney outcomes associated with eGFR and albuminuria. Aim 3. To develop risk calculators for CKD incidence, CKD progression, and ESRD overall and in specific populations such as patients with heart failure. In all aims, we will continue to implement and expand upon our innovative meta-analysis methods, including Markov processes, simulations, and standard incorporation of competing risks. We remain flexible and efficient in responding to high priority topics set forth by guideline organizations (e.g., Kidney Disease: Improving Global Outcomes), regulatory agencies (e.g., US Food and Drug Administration) and major societies (e.g., International Society of Nephrology, National Kidney Foundation, and American Society of Nephrology) as well as informing global health metrics and economic efforts (e.g., Institute for Health Metrics and Evaluation Global Burden of Disease). Our overarching goal is to advance the understanding, care, and outcomes of CKD patients and global populations, using an investigator-led global consortium and the data and expertise from ~300 international collaborators.